Multipole Corrections to Account for Structure and Proximity Effects in Group Contribution Methods: Octanol-Water Partition Coefficients

Shiang-Tai Lin and Stanley I. Sandler
Center for Molecular and Engineering Thermodynamics
Department of Chemical Engineering
University of Delaware
Newark, DE 19716

Abstract
We propose a new method to correct for structure and proximity effects that are not generally taken account in group contribution models. Molecular orbital calculations for isolated molecules are performed to obtain the net charge and dipole moment on each group within the molecule. These group multipoles, which vary due to the presence of proximate groups, are used as the basis for corrections to simple group contribution methods. We have applied this method to our recently developed GCSKOW model to predict the octanol-water partition coefficients (KOW) for complex molecules. We studied this simple, theoretically-based method with a total of 322 solutes, including five pharmaceutical compounds. The root-mean-square (RMS) deviation in the log10KOW calculated from the GCSKOW model with these multipole corrections is found to be 0.16 (which leads to a mean error of 44% in KOW), compared to a RMS deviation of 0.42 (163%) when no correction is made. This approach is much more accurate than the KOW-UNIFAC model (RMS of 0.46 or an error of 188% in KOW) and also better than ClogP (0.19 or 55%), which heretofore had been considered to be the most accurate predictive method for octanol-water partition coefficients.
 
 

Last updated on January 28, 2000.
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Critics or comments: stlin@udel.edu